1.Structural basis of heteromeric amino acid transporters and advances in targeted drug development
Lu DAI ; Chenye XU ; Xiaoting WANG ; Hao LIANG ; Shuo ZHANG ; Renhong YAN
Journal of China Pharmaceutical University 2026;57(4):422-433
Heteromeric amino acid transporters (HATs), formed by the assembly of solute carrier 3(SLC3) and solute carrier 7(SLC7) family members, play essential roles in amino acid transmembrane transport, cellular nutrient sensing, and redox homeostasis. Dysregulation of multiple HATs members has been closely associated with tumor metabolic reprogramming, ferroptosis resistance, and inherited amino acid metabolic disorders, making them important targets for drug development. However, the high conservation of substrate-binding pockets, the limited druggability of zwitterionic compounds, and safety concerns arising from their broad expression in normal tissues have collectively hindered the clinical translation of HATs-targeted therapeutics. Recent advances in cryo-electron microscopy (Cryo-EM) have enabled the determination of high-resolution structures of multiple HATs, providing a critical foundation for understanding their molecular mechanisms and for guiding targeted interventions. These structural studies have systematically revealed the molecular basis of selective substrate recognition and ion coupling among different family members and have identified non-conserved structural features that may serve as potential opportunities for subtype-selective targeting. In this review, we systematically summarize recent advances in the structural biology of HATs, with a particular emphasis on their assembly mechanisms, substrate recognition modes, and conformational transitions. Furthermore, we highlight recent progress in structure-based drug design (SBDD), including strategies to enhance ligand affinity by exploiting non-conserved hydrophobic side pockets, as well as approaches to block the transport cycle by disrupting the secondary structures of transmembrane helices TM3 and TM10. Collectively, these insights provide an important structural framework and new perspectives for the development of highly selective inhibitors for HATs and related therapeutic strategies.
2.Level of hope and its influencing factors in elderly patients with total knee anthroplasty
Qingbin DING ; Yanping JI ; Meihong CHEN ; Yan SUN ; Xiaoyuan WANG ; Renhong TANG ; Honghong ZHOU ; Yanshuang LI
Chinese Journal of Modern Nursing 2019;25(25):3257-3261
Objective? To investigate the hope level of elderly patients undergoing total knee arthroplasty (THA) and analyze its influencing factors, so as to provide evidence for improving the hope level and quality of life of patients after THA. Methods? A cluster random sampling method was used to select 308 patients with bilateral THA for the first time who were admitted to two ClassⅢ Grade A general hospitals in Harbin from January 2017 to July 2018. Questionnaire surveys were conducted using Herth Hope Scale, the Second Edition of Beck Depression Scale and Social Support Scale. Results? The total score of hope level in elderly THA patients was (29.96±8.72). Among them, 76.62% (236/308) had moderate to high level of hope and the total score of depression was (19.20±11.75) which was at a moderate level. There were significant differences in the hope level of patients with different gender, place of residence, educational level, marital status and family per capita monthly income (P< 0.05). The results of multiple stepwise regression analysis showed that age, sex, family income per capita, depression, negative coping style, subjective support and objective support were the influencing factors of elderly THA patients' hope level (P < 0.05). Conclusions? The THA patients' hope are at a medium level. Medical staff should pay attention to the relevant factors affecting the level of hope, adopt targeted nursing intervention measures, give psychological guidance to patients, provide social support, and further improve the level of hope of the THA patients.

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